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Comments: 104 • Responses: 40  • Date: 

electric_onanist161 karma

MD here. Is there any published peer-reviewed research that supports better health outcomes for patients who use your technology?

There are plenty of quacks and noctors in my line of work who routinely order lots of unnecessary or dubious blood tests and call it 'medicine'. Because it helps the patient to feel important and cared for, but is actually useless for improving health outcomes. A really common thing for them to do is interpret these test results as 'evidence' the patient needs to buy overpriced and useless supplements from the noctor.

You really seem like you're offering more of that. Happy to be proven wrong if you have any evidence.

iollo_health-24 karma

There are several studies now that are starting to translate metabolomics findings from mere scientific results to actionable interventions. Here are some examples from large research studies:
Type 2 Diabetes and interventions
https://journals.sagepub.com/doi/10.1177/0840470420904733
Behavioural coaching for general wellness
https://www.nature.com/articles/nbt.3870
As example for a very specific, single marker, 2-hydroxyglutarate in blood can be evidence for cancer:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682342/
Also, longitudinal studies of health aging indicate that repeated sampling can identify individuals who are on a detrimental trajectory:
https://www.nature.com/articles/s41591-019-0719-5

toyboxer_XY51 karma

As I'm sure you're aware, showing an association in a population study is not the same as demonstrating causal relationships exist, communicating increased risk to individuals is difficult even when this is done by trained counsellors, and there are significant confounders (like ancestry/ethnicity) that need to be controlled for that your cited studies don't have data for.

How do you intend to address the challenge of communicating "results" to patients when interpretation at an individual level is difficult-to-impossible, the evidence is extremely flimsy, and there may be no way to address a metabolic finding?

There are some serious ethical (and probably regulatory) issues around providing "wellness data" to people while citing actionable health insights based on lab tests.

At the end of the day your site lists "results" like "you told us you sleep on average 7 hours per night", recommending that the person sleeps more, or step count measurements that have nothing to do with blood sampling.

Is this meant to provide value that a cheap smartphone can't?

iollo_health-33 karma

We agree this is a sensitive topic, and we'll make sure every aspect reported back to the users has solid research backing behind it and is flagged if there are any known imprecisions.

rob_shi101 karma

Neither of y'all worked at Theranos right?

I'm joking of course. However, did that scandal, combined with the recent downturn in venture capital funding, put a damper on your prospects?

Best of luck!

iollo_health49 karma

Thanks for addressing the elephant in the room 😄 We have nothing to do with Theranos.

We already have the technology (mass-spectrometry), which is widely used by universities and pharmaceutical companies for research purposes. Using such established methods avoids the use of custom-made machines and builds on decades of research before.

During Theranos, companies were challenged how they could do it better than Theranos. Immediately post-Theranos, investors were rightfully skeptical of the space. Now, investors (and regulators) are doing better diligence. A lot of investment has returned and grown in this space in recent years with lots of advance in technologies across the board. Here's a nice write up from Nature: https://www.nature.com/articles/s41587-022-01242-0/

The recent downturn in the market is a concern for all companies right now, but Seed and Series A markets seem to be less affected. Nonetheless, some of the best companies started during the 2007/8 financial crisis. Look at Airbnb 🙂

Enoxitus48 karma

Why is this worth $109 a month (recommended option)?

iollo_health-69 karma

Great question. Clinical labs charge $400 per test or more to measure around 30 markers, like glucose, HDL, LDL, etc. For $109 a month, we measure around 650 markers (20 times more than what you typically get) and this is done 6 times/year. Those 650 markers are now known to associate with more than 25 age-related chronic diseases (source: https://www.nature.com/articles/s41591-021-01266-0)

Krisblade220 karma

This comment is why as someone who works in the field of proteomics and metabolomics in relation to Alzheimer’s disease that I honestly think it’s shameful how you’re promoting these tests. “More” doesn’t mean better - you’re comparing clinical viable well research tests with bio markers we haven’t even sufficiently researched to make clinical statements about. Research medicine and clinical medicine aren’t at the same standard, we don’t disclose research results to participants for this reason - we don’t know enough about what those levels mean to actually tell someone how to interpret them.

We can explain with decades of research and clinical evidence what raised glucose or lipid profiles mean, we cannot do this with metabolomics because we literally do not know. We are just throwing darts in the dark and trying to work out what it all means. Even the papers you linked elsewhere were tiny trials on 20-30 people with vague outcomes. To suggest these results will be clinically relevant is laughable, it’s going to be a badly hashed AI with half complete data telling people vague results.

I spend millions on metabolomics on thousands of samples a year as we have a biobank of 300,000 samples from over 5,000 participants. I wouldn’t get this test because we can’t actually say what the results mean, that’s what we’re researching! Claiming you can interpret such a new field of research with an algorithm is honestly worrying. And I also agree with others that I fail to see what the benefit would be of getting these results 10+ times a year. They’re clinically irrelevant anyway. It’s fine if people are curious and understand we can’t really interpret the results but that’s not what your advertising. This is just some half hashed algorithm, we can’t interpret these the way you claim and you’re pushing the limits of what you can claim.

iollo_health-6 karma

A lot to unpack here, and we appreciate the critical dialog. We will reply both, to the more consumer-oriented comments as well as to the scientific criticism.

First, we agree that sheer number of measurements does not immediately equal “good”. If all of this was just noise, even 100,000 markers would not do anything. But that is arguably not the case for blood metabolomics measurements. 15-20 years of research in the field going way beyond our own work have shown that the blood metabolome is a very deep and rich profile of various aspects of human health and disease. The published studies we are drawing our information from are substantially bigger than tiny trials on 20-30 people, with some of them including thousands of participants.

Statistical confidence in the associations in such studies has nowadays reached levels that, with careful evaluation, will go well beyond throwing arrows in the dark. Importantly, many studies of the last few years go beyond simple associations of some cryptic blood molecules with disease states, but have started to go into real precision applications mapping blood measurements to health status.

Research medicine and clinical medicine are indeed not the same standard. We also agree that people need to not be supplied with vague statements based on noisy data. That is why we are carefully and systematically curating every single aspect that is being reported back to the users. For example, in the early phases of our company, we are making sure to not simply throw potentially false positive disease diagnoses based on unclear data at the people, until the underlying science and statistical evaluations are 100% solid.

Regarding your own research, with the sample size you are mentioning, you have one of the larger biobanks in the world, certainly at the top end of metabolomics research. We would love to chat more with you to have a critical debate about the scientific underpinnings of our concept.

red_concrete72 karma

A lot to unpack here

There really was not a lot to unpack there. You sell a package of longitudinal measurement of many biomarkers, with no valid justification for why more, nor why these, are better for prediction of disease risk. There is far too much uncertainty. I would be surprised if you obtained any R2 value over 0.15 (the publication you linked up-thread doesn't even report them). You may have confidence in the associations (I can't comment), but that says next to nothing about predictive ability.

We would love to chat more with you to have a critical debate about the scientific underpinnings of our concept.

I'm another guy here, but here you go... An AMA is a perfect venue for such a chat.

EarlDwolanson16 karma

Yes - statistical differences do not equal predictive power for diagnosis/prognostics.

iollo_health-4 karma

Fully agree. We will evaluate each individual case for actual predictive power, not just significant p-values.

iollo_health-2 karma

There are certainly metabolites with low values of explained variance, but also reports on various traits with much higher R2 values (up to R = 0.83) than those (source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294785/). Our current R&D is to identify exactly those cases, and work those out in the reports iollo will be generating.

la_peregrine48 karma

I am rather unappreciative of the carelessness of the numbers here.

Presenting 400 per test vs 109 per month would make it seem that you are roughly 4 times cheaper. But since you are testing only 6 times per year which means you are charging 218 per test, you are only roughly 2 times cheaper.

I also do not think you quite address the question, and I'd really like it if you did.

Could you answer the question why we need an answer every 2 months instead of say every 1 yr or 5 yrs or 10 yes? Because your test being twice cheaper while measuring more stuff doesn't explain why we need so many measurements per year. It would be nice to know what making these measurements on say every 10 years give, then what more you'd learn if you test every 5 yrs, every 1 yr, every 6 month, and finally why it is worth it every other month as you are advocating here.

iollo_health6 karma

Really appreciate the comments. 🙏 We are responding to several of the critical comments from this sub-thread, and hope we can provide clarification. Note that we slightly changed the order in which they appeared:

“If I take my blood first thing in the morning vs after I have had my biggest meal of the day there would be a world of difference. And same if I took it the day after a feast vs before etc etc.”

That is exactly right, and a well-known issue that needs to be addressed when performing metabolic measurements in blood. First of all, the current fasting status has a major impact on the measured values. Thus, we instruct users to always take their sample in the morning, after at least 8-10 hours of overnight fasting. This is an established procedure to remove unwanted variation, and has been used in many large-scale research studies around the world. Regarding your second point, effects of your food that might last more than just overnight, this is exactly one aspect of what we are looking for with our test. If it lasts for more than one day, it is likely related to your overall dietary pattern, and might already influence your fitness and health status for the better or the worse. We also capture dietary intake before and during the sample collection to account for these foods.

“Could you answer the question why we need an answer every 2 months instead of say every 1 yr or 5 yrs or 10 yes? [...] It would be nice to know what making these measurements on say every 10 years give, then what more you'd learn if you test every 5 yrs, every 1 yr, every 6 month, and finally why it is worth it every other month as you are advocating here.”

“I get what the science is achieving by averaging. I don't get what the consumer is getting.”

“Their plans seem really arbitrary in the cost for the return and the number of tests. Not sure how they came up with it but hopefully op will give us some response.”

As both of you correctly mentioned, an essential aspect of monitoring your personal status is your own baseline and relative changes. Averaging across many samples that we will collect is a very interesting way to build up our own knowledge base for the future, but indeed not the main benefit to the consumer. Rather, we believe that a fine-grained assessment of your personal trajectory, through healthy times and disease, through regular daily life and unexpected changes, through times of activity and inactivity, and potentially through the seasons of the year, will help us know what you look like normally. This in turn will then allow us (a) to see if things are not going well for you anymore and drifting apart, and (b) to monitor potential lifestyle interventions such as an increase in physical exercise or dietary changes, and see the results right away.

Now, admittedly, whether this needs to happen every 3 months, every 2 months, or every month is still up for debate. That’s also why we offer different packages, where people who are more skeptical can start with a smaller version, and people who are very interested in a fine-grained analysis of their personal profiles can go for the premium packages.

la_peregrine15 karma

I appreciate your response.

we instruct users to always take their sample in the morning, after at least 8-10 hours of overnight fasting. This is an established procedure to remove unwanted variation, and has been used in many large-scale research studies around the world.

...

Now, admittedly, whether this needs to happen every 3 months, every 2 months, or every month is still up for debate. That’s also why we offer different packages, where people who are more skeptical can start with a smaller version, and people who are very interested in a fine-grained analysis of their personal profiles can go for the premium packages.

True and if this was IAmA about cool research or non-profit research study I'd accept it. However, this is an IAmA about "iollo (our startup) to give you a new way to understand your health and aging by measuring 500 blood metabolites." From that perspective I expect you to have a handle on what would a consumer get with what frequency of studies. This is definitely not something that the average consumer should be expected to do. Furthermore, to make recommendations you have to know on what scale variability is relevant for what condition. For example, every two months is vastly inadequate to monitor bun and creatinine for CKD purposes but is overkill for the average person concerned with general aging or some unrelated condition. Even young male with proteinuria suggesting monitoring for IgA nephorpathy, the standard of care is not a test every 2 months but much less. So every 2 months may not be a premium product if every 2 months is unnecessary and does not provide information. To provide a different example of the concept -- if i am interested in weather then atmospheric moisture level every 15 min may be useful but if I am interested in long term climate, such measurement will be noise and the first step would be to average it out.

It is against this subreddit rules to ask the same question but to me you have NOT ANSWERED THE QUESTION on what time scales do the different markers that you measure and the different conditions that you make recommendations about require monitoring.

iollo_health-10 karma

This is great input. We're constantly improving on that. Each testing frequency does bring different types associations and granularity to the the reports you receive.

pelmag6 karma

Slightly off topic, but why are the prices for basic blood tests you both quote so insanely high? The same tests in Europe (done on US machines and reagents, labs are required to report it to the customer) would be in 2-5 eur range. Wouldn't that constrain the technology to US market only?

iollo_health-1 karma

The actual costs of standard labs are opaque from the top US labs (LabCorp, Quest Diagnostics). The cost to the individual is even more complicated due other variables of our healthcare system. The price the individual pays varies due to many factors, insurance company, insurance plan, location, age, insured, non-insured, in-network, out-of-network, no deductible, high-deductible, preventative, indicated or elective, copay, co-insurance, and the list goes on. It's difficult to provide a very precise answer around what an individual will pay for a given lab because it is all dependent on the variables above.

None of the above include the cost of the appointment with your doctor to be prescribed the labs, draw the labs, time and travel costs for both of those.

What we can do is compare the list of metabolites we measure in one of our tests compared to what you would typically get from standard labs and the prices Quest (https://questdirect.questdiagnostics.com/products) and Labcorp (https://www.ondemand.labcorp.com/catalog) provide. We recognize, it's not a perfect comparison and we will work on documenting and publishing how we established our comparison so it is more transparent.

I can't speak about the European market, but our tests are available only in the US.

A few things are clear: our current healthcare system does a good job for certain things and a bad job in others. There is lots of room for improvement on how we learn about what's going in our bodies and the potential impact of the things we do with them in terms of what we measure, process, cost, and transparency. It won't be for everyone and every circumstance but will be developed and made available as the technology, science, and regulation allows.

I think we can all agree, there is room for improvement 🙂

EarlDwolanson1 karma

Are you measuring the 650 markers mentioned there? If so, are you outsourcing your samples analysis to Metabolon? How do you ensure data is comparable over time?

iollo_health-1 karma

We're currently working with a different assay that is not by Metabolon which has a large overlap of coverage. We use a quantitative assay (vs Metabolon's untargeted approach) that ensures comparability of data over time.

Missing_tooth39 karma

How do you manage and communicate the potential for false positives when performing 500 unguided tests monthly on the same patient?

iollo_health-22 karma

Thanks for asking this. It is a very important topic.
Let us start out by saying that the more impactful a result will be for a person, the higher the confidence needs to be, and we are very aware of that. Diagnosing someone with a specific disease requires very high confidence, i.e. both low false positive and low false negative rates. That's also why disease diagnosis will not be the focus for the first generation of iollo. General assessment of healthy biological aging and overall fitness status allows for more variation, and research papers have confirmed positive results there. That is what we will focus on in the beginning, while tackling the bigger questions.

WorkyMcWorkmeister27 karma

Will you protect patient privacy or will you be selling the data results of your tests to pharmaceutical/insurance companies?

iollo_health6 karma

We are HIPAA compliant, meaning all of your protected health information (PHI) is encrypted and kept safe. Your information, results, and recommendations will never be shared with employers or insurance companies.

You can opt in to participate in scientific research, like drug discovery, only using your anonymized data, but it will not be shared without your consent. And we will only select research that would also benefit those taking the tests, ie. help you live longer or healthier.

Our subscription plans will sustain and allow us to grow to help more people without having to sell your data.

klontjeboter42 karma

Then why does your privacy policy state that iollo has the rights to use anonymized metabolomic data and self-reported data for scientific research, including disclosure to third parties?

I'm not trying to have a "gotcha" moment here - maybe you just accidentally gave yourself too much legal leeway in your privacy policy

For scientific research. We may include your anonymized metabolomic data and self-reported information in disclosures to third parties for the purpose of research or other applications, but no identifying information will be shared without your prior knowledge and consent. iollo research is intended to advance science and knowledge and to create, commercialize, or undertake activities toward the practical applications of this learning to the improvement of longevity, health and healthy lifespans. Research may be conducted by our own team, or by our research partners, which may include commercial or non-profit organizations that conduct or support medical research or conduct or support the development of drugs or devices to diagnose, predict, or treat health conditions. Our Research Consent document outlines the details of our research and analysis.

/u/workymcworkmeister

iollo_health35 karma

Thanks for identifying this! It is out-dated language from our legal team that needs corrected.We are consulting them now to update this.

[Edit] The Privacy policy is updated to reflect our commitment to your privacy. Thanks again for finding this one.

iollo_health-1 karma

Thanks for catching this! It is out-dated language from our legal team that needs updating.
We are consulting them now to update this.

Olmansju21 karma

Can you talk about your different plans? They seem to be very oddly priced and laid out. A single test per year is $23 a month but you only take the test once And receive what appears to be minimal information about the results. Psychologically, how is that a monthly plan? what other useful information do you get throughout the year? Can I use my HSA money to pay for the test? If so I probably need to pay per test, and have the test requested by my doctor.

iollo_health-15 karma

Thanks for the questions!

The price per test goes down the more tests you do. We show a monthly price because that's what people are most familiar with for subscription plans. It sounds like we have some room for improvement here, appreciate your feedback 👍

The real benefit of this test is doing it more than once. As you test more often, we'll be able to see how your metabolites are changing and what they associate with in your everyday life, like diet, physical activity, how much you sleep, stress levels, the products you use(lotions, shampoo, etc), supplements, and medications. Based on these, we'll be able to provide you with highly targeted recommendations based on your profile. Also, we can accurately calculate how fast you age, which is now known to be an indicator of overall health, source: https://pubmed.ncbi.nlm.nih.gov/29340580/). Because this might not be immediately obvious when you are picking a plan, we incentive multiple-test subscriptions.

While you have a subscription, you can benefit from new analysis we are able to perform. For example, in the future, when there is sufficient evidence and regulatory approval in place to do so, we could also show associations with certain conditions. A more current example would be as we improve our dietary recommendations, you could log back in and see what the improved recommendations are.

Unfortunately, we can't accept HSA today, but we working on it.

shwag94532 karma

This seems more like you are just gamifying healthy habits with marginal benefits over your typical doctor's visit or other services like professional (hospital-associated) nutritionists.

Dollar-per-dollar how much of an improvement on existing services does your service provide?

iollo_health-3 karma

This is a good question and we appreciate this feedback. While we are convinced of the significant added value of metabolomics measurements, we are actively quantifying the per dollar added value of our tests, which will be much clearer soon.

xplac3b010 karma

Are you doing this off a high res ms1 qtof or are you using an orbi and collecting ms2 or? Are you doing quant and this is all an mrm panel? Are you doing multiple runs to hit multiple species(ie pos, negative on both c18 and hilic)? Did you guys build out the library using IROA or how was the workflow built out? Just curious as I'm starting to look at expanding passed my proteomic runs into metabolomics for my own research. Thanks for taking the time to introduce people on reddit to metabolomics!

Edited since I saw you said you do 650 analytes in another response.

iollo_health4 karma

Awesome to have another fellow mass spec person here! 🙌
We're doing this using TQS, an MRM panel and it's fully quantitative. We're also doing multiple runs to hit multiple species and running both positive and negative modes on C18 columns. Definitely an exciting way to expand!

lorazepamproblems6 karma

I'm familiar with the biomarkers you mentioned (glucose, dopamine, vitamin D, cholesterol, fats, hormones), but I had never heard of them referred to as metabolites before. My understanding is that a metabolite is a breakdown of a drug or other chemical in the body. Where does this broader usage of the term come from?

Second question: Are you collecting info on people's 500 metabolites in order to discover associations with diseases you can help diagnose (meaning test for markers and do long-term follow up) or do you already know what the associations are?

Last potpourri question: What is a very interesting metabolite most people including my PCP have probably never heard about that you think is important to test for?

Edit: I didn't read well enough--you already answered my second.

So I'll ask another: Why do you think fasting insulin isn't used more as as marker for pre-diabetes and diabetes? I've read very interesting research showing high fasting insulin is a great marker for diabetes even when FBG is normal. My doctor was very reluctant to test but surprised at the results. Do you look at this?

iollo_health4 karma

Thanks for the great questions!
(1) The word "metabolite" comes with slightly different meanings in the field. First, the product of the degradation (metabolization) of a compound, such as a drug, can be called the metabolite of that compound. That is exactly what you are referring to.Second, the word "metabolite" just means "biochemical molecule". That includes all the sugars, vitamins, amino acids, fatty acids, lipids, food components, energy products, and so on, that we can see in your blood stream. The entire set of metabolites is called "metabolome", and the technology to measure it is called "metabolomics".
(2) First of all we have to state that at this point in time, iollo does not diagnose disease. We provide insights into the status of your health with respect to certain organs, food patterns, and your natural aging process.That being said, medical applications, such as disease diagnosis, are certainly part of our future plan. At that point we will do both, rely on published studies as you mentioned, which is the safer starting point; but also discover our own, new markers as soon as the number of datapoints we collected allows for new discoveries through our research.
(3) It's hard to pick a favorite among all the interesting metabolites out there. A very interesting biochemical compound is 2-hydroxyglutarate. It gets produced at high levels by certain tumor cells that have a defect in their energy metabolism, and could be used in future versions of iollo to detect cancers early.(Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682342/)

iollo_health-1 karma

Regarding the fasting insulin question:
There was a recent, seminal paper by scientists in Sweden, which defined various subgroups of diabetes based on different variations of insulin resistance, glycemic indices, as well as BMI and age. Importantly, these groups significantly differ in terms of diabetes complications and treatment options. Researchers from Qatar and New York are currently working on exploring the blood metabolomics component of these clinically-relevant subgroups. Once those results are officially published, we will look at the potential of using them in the iollo platform.

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30051-2/fulltext#%20
Which is paywalled, below a free preprint:
https://www.ludc.lu.se/sites/ludc.lu.se/files/ahlqvist\_lancet\_diabetes\_endocrinology\_2018\_accepted\_version.pdf

red_concrete20 karma

In my circles (medical statistics) that clustering paper was quite widely derided. I wasn't aware anyone considered it seminal. Do you have statisticians on staff that assist you with critical appraisal?

iollo_health0 karma

Fair point in general. High profile paper, lots of scrutiny.
If you tell us what the specific points were that you were questioning, we're happy to discuss.
Regarding your question: Yes, we are computational biologists with formal training in statistics. We widely applied statistical methods on various datasets, and have developed and published a few methods ourselves.

crappysurfer5 karma

To what degree is your product predictive or diagnostic? My understanding of many (fringe) chronic illnesses is that the molecules are not defined in medicine which make diagnosis challenging. Do you have any plans to seek out tests that identify or quantify currently undefined molecules that could be in association with chronic illnesses that have poor (or non existent) treatment modalities simply due to poor understanding/research/medical resolution?

Right now the diagnostic tools for the conditions you've mentioned already have relatively inexpensive tests for diagnosis. What is the primary benefit for the consumer when it comes to your product?

To what degree is this crowd funding biological data collection versus a practical tool?

iollo_health-2 karma

At the beginning we will only be focusing on the associative aspects of our product and over time we plan on moving into prognostics and diagnostics. Yes, we do have plans to seek out unidentified metabolites that associate with different illnesses that have poor/non-existent treatment.
Right now, the main benefit is with our tests, you'll be able to find associations between your everyday habits, like diet, physical activity, stress level, supplements, products, and more with your metabolite levels and also see how fast you're aging, which is an overall indicator of health. In the future though we do plan to expand to diagnostics.

Pinewood265 karma

Are you by chance a member of here comes treble?

hell0potato3 karma

Have you seen specific results for T1 Diabetics? What about people who take metformin?

iollo_health3 karma

Research studies by us and other colleagues have shown specific metabolite patterns associated with the onset and progression of Type 1 Diabetes, as well as the development of certain complications. (see study links below) Overall, as for many other things, there is a lot to learn about Type 1 Diabetes from metabolic profiling in blood.
Regarding metformin: In an ideal case, your blood will look normal again after you take the right medication for a disease. In practice, not everything will be perfect after medical treatment, however, and blood tests can help monitor health status over time.
References:
https://www.mdpi.com/1422-0067/20/10/2467
https://www.nature.com/articles/s41598-018-32085-y
https://link.springer.com/article/10.1007/s11892-016-0820-9
https://link.springer.com/article/10.1007/s00125-018-4688-x

fyodor_mikhailovich2 karma

Is there anything on the horizon in your field that could improve allergy detection by blood tests? Or do immunoglobulin proteins not fall within your purview?

iollo_health2 karma

It's definitely something we want to do in the future (I (Dan) actually suffer from allergic rhinitis) though we already do measure metabolites that contribute to immune response and inflammation like histamine, dopamine, arachidonic acid, TMAO, long chain acylcarnitines and more. We're planning to expand our panel coverage too down the road, beyond metabolomics.

chuckchange2 karma

Any fecal testing or cross referencing with other labs/tests?

iollo_health2 karma

At this point in time, we're not collecting any fecal samples, though there are other companies that focus on this awesome topic. Also we're definitely checking how the metabolites we measure correlate with clinical labs/test.

TransposingJons2 karma

Thanks for the AMA! Are there any "new" blood components that seem interesting and that we are just learning about?

iollo_health1 karma

We're constantly expanding our knowledge about blood components and what they represent.
This includes, one the one hand, new metabolites that scientists weren't aware of before. This is called an "unknown" metabolite, and there is an entire research field behind this. Estimates of the number of metabolites out there go into the tens of thousands, maybe more.
On the other hand, we learn more and more about molecules that we've known for a long time, such as sugar and amino acids, where new studies show that they might provide information about health status, dietary status, all the way to the question whether a given disease treatment will work for a person or not.

bristle_health2 karma

Very cool! Do you also provide guidance on how to improve/modify the metabolites that you measure? What types of behaviors/interventions have been found to impact our metabolome as it relates to aging and chronic disease?

iollo_health6 karma

Yes we do! We match individuals with dietary and behavioral (and in the future, therapeutic) interventions based on the 500+ metabolites that we measure in the lab.

Almost all known medical interventions impact our metabolome in relation to aging and chronic diseases. Some well-studied interventions include the DASH diet [1] (which reduces the risk for heart disease), fasting [2, 3], targeted physical activity [4], statin intake [5], metformin [6] medication (which has been shown to extend healthspan and lifespan), and many more.
References:
[1] https://academic.oup.com/ajcn/article/108/2/243/5038205
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412259/
[3] https://pubmed.ncbi.nlm.nih.gov/32931723/
[4] https://www.cell.com/cell/fulltext/S0092-8674(20)30508-0
[5] https://www.ahajournals.org/doi/10.1161/CIRCGENETICS.117.001759
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508882/

WertyGDB2 karma

How many results will we get?

iollo_health-1 karma

It depends on which plan you subscribe to. Each test contains one report, so for the 1 test/year, you get 1 report, and for the 9 tests per year you get 9 reports. After your first test, we'll be able to provide you with your personal metabolite trends which associate with your everyday life, like diet, physical activity, medication, etc. and calculate how fast you're aging, which indicates how healthy you are and potentially how likely develop a age-related condition (source: https://pubmed.ncbi.nlm.nih.gov/29340580/).

In each report, we analyze over 500 metabolites. You can see those here if you're interested: https://www.iollo.com/whats-measured.

la_peregrine3 karma

The link you provided only 10 and the rest are in an article behind a paywall for the average person. Would you please provide a non-paywalled version of the article?

iollo_health3 karma

Definitely. Here is an accessible link to the paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175034/

la_peregrine4 karma

Sorry I was unclear. What I meant to say is that the link you provided here:

In each report, we analyze over 500 metabolites. You can see those here if you're interested: https://www.iollo.com/whats-measured.

lists only 10 marker and then links to a paywalled nature article "Plasma metabolites to profile pathways in noncommunicable disease multimorbidity"

This is the one I was asking about. The other article (J Gerontol A Biol Sci Med Sci) is addressing 20 markers, rather than the 10 on your website, but that is a far cry from the 500-ish you are talking about.

iollo_health3 karma

I see what you mean now. It's updated. Thanks for pointing it out 👍

maybeinoregon2 karma

How does having a metabolic myopathy effect your test?

iollo_health1 karma

As you certainly know, metabolic myopathies can have very severe symptoms, with a substantial impact on the person's health. In the long term, iollo might provide beneficial information for people with this disease. However, for now, this is a condition that needs to be tightly monitored under the direct supervision of medical doctors.

Pyrrolic_Victory2 karma

Hi, fellow instrument chemist here (huge huge nerd for it, and lucky enough to work in a lab with >10 high end mass specs) and love what you’re doing. I do some human exposome work and I always think we should add this type of analysis to pesticide/POP stuff we do.

What brand and type of instruments do you use? Do you do any gcms and do you use Mass labelled isotopes for internal standards for every compound?

Also have you looked into using analysers like orbitraps to cut down the number of injections needed while still remaining quantitative? I’d be very interested to see the métabolomes reaction to various exposure scenarios of pollutants/PFAS/microplastics etc.

Finally, do you use GCMS at all?

iollo_health1 karma

Hey fellow instrument chemist! We use Waters and Sciex, for measuring metabolites quantitatively. We don’t use radiolabeled compounds for each compound but do run a 7 point calibration standard curve using analytical grade standards.
We do have a couple of orbitraps and have just purchased a new high end one coupled with a Vanquish.  We are developing radiolabeled methods for a large number of metabolites (larger than our current panel) but they are still under development and will be ready in the future. As for the last part of your question, that would be a very nice study indeed.
 
We do have GC-MS in the lab, but it is mainly for head space analysis and flux studies.

EarlDwolanson7 karma

So to be clear, you currently do not use isotopically labelled standards? I am strugling to understand if you are producing absolute quantification results or relative abundances with your workflow.

iollo_health-2 karma

To clarify, we don't use isotopically labeled standards and instead we use a 7 point calibration standard curve using analytical grade standards to produce absolute quantification.

globaloffender2 karma

Are you only interested in metabolic markers or will you consider other targets like cancer? Next gen sequencing is the future of medicine (see PGDx, illumina, thrive, etc) so you’ve picked a great starting point

iollo_health1 karma

Thanks! Great question. Many metabolic markers now associate with different types of cancer and. next gen sequencing technology is definitely helping with that.

M3Z5G99A30V21AML92371 karma

Thoughts on allergies/hayfever and what are things people suffering from them can focus on?

iollo_health1 karma

This panel is not specifically designed for allergies/hayfever at the moment, but we do measure metabolites related to immune response and inflammation that may be useful.

iollo_health1 karma

!lock

Emergency-Ad1604-1 karma

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iollo_health0 karma

Thanks for sharing the love u/Emergency-Ad1604 :) We're happy to help!

ninthpower-1 karma

Dr. Krumsiek I took a course from you at Cornell a few years ago and enjoyed learning about you're work!

Question: I have a family member with Crohn's Disease and many people suffer from other IBD/IBS-type conditions. How has metabolomics played a part/will play a part in treating these kinds of conditions? What are some unanswered questions that you hope can eventually be solved with metabolomics?

iollo_health3 karma

First of all, glad to hear that you enjoyed my course and our research in general!
IBD/IBS: First, I have to declare that these conditions are not a direct research focus of our academic lab. It is my understanding that the metabolomics field for these particular type of bowel disorders is mainly focusing on novel diagnostics and potential disease monitoring. It does not seem like the actual treatment of IBD/IBS seems to be in the focus of metabolomics research.
I'm sure you have looked into the background literature yourself already, but I'm linking some review papers below:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625096/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721420/
Unanswered questions: Regarding the blood metabolome and iollo, it has become more and more clear that circulating metabolites carry a systematic footprint of various diseases and conditions, as shown by a vast body of literature that has been published over the past two decades. There is a lot of work ahead of us to pinpoint the specific items we can report back to a user, but the potential is very large.
Regarding metabolomics in general, apart from blood sampling: There are many other potential applications, for example in the profiling of cancer escape mechanisms and combination drug disease, where we have data proving that metabolomics can play a major role.

Shambling-1 karma

Any thoughts on the work of William Walsh on the epigenetics and metabolism of brain function and disorders?

When can I get your tests in UK?

Have you heard of projects like the personal genome project and nebular genomics and their overlapping work integrating functional testing, like; genomes, epigenomes, microbiomes and ideally metabalomes?

iollo_health1 karma

Dr. Walsh has published milestone papers in the field of neuroscience. Epigenetic imprinting is certainly a field of high importance for various diseases, for example, as it carries the long-term exposures you have accumulated over your lifetime. Our academic research specialization is on probing brain metabolism using metabolomics data, but we are also cross-referencing it with other omics layers, such as proteomics, and epigenetics.

Our current focus is on the US, but we expect to make the tests available in the UK in the near future (2-3 years). Although if you ever do visit the US, we can help you coordinate to test with us!

Yes, we’ve heard of both the personal genome project and nebular genomics. Both are doing great things in the field of genomics and we’re looking excited to see how they would be integrating other types of biological data into their current platform.